Novel phthalocyanine nanowires and uses therefor

ABSTRACT

M-phthalocyanine nanowires according to the present invention can have a variety of uses as the M-phthalocyanine nanowires can control the crystalline structure thereof by controlling the flow speed of a carrier gas to a suitable range, and can exist in hydrophilic solvent without agglutinating due to superb dispersibility in water.

TECHNICAL FIELD

The present invention relates to novel phthalocyanine nanowires and uses therefor.

BACKGROUND ART

The control of a crystal structure of organic and inorganic crystals is an important requirement for systematic studies of polymorphic crystals. Among various crystal growth methods, the PVT method, which is widely used to grow numerous organic and inorganic crystals of various dimensions, including ZnPc NWs, has been considered difficult to grow crystals in a selective structure. This is because the crystal structure of the crystal is usually fixed with intrinsic properties determined mainly by thermodynamics, and the PVT operates at a fixed temperature with various dynamic parameters.

It is very common to have one or more polymorphs in organic and organometallic molecular crystals due to diverse and weak non-directional intermolecular van der Waals forces. In particular, polymorphisms of several phthalocyanines with various weak interaction sites have been widely studied due to their different electrical and optical properties depending on the laminated structure. For example, α-phase titanyl phthalocyanine exhibits 250-750 times higher mobility than β-phase titanyl phthalocyanine due to interlayer electron coupling. In addition, the different π-π laminated interactions of triclinic and monoclinic lead phthalocyanine exhibit different Q-band absorption properties, which means that the electronic structure of lead phthalocyanine may be easily controlled by changes in the laminated structure. Among various phthalocyanines with polymorphic structures, the target molecule ZnPc has received much attention as a promising photosensitizer for cancer phototherapy. ZnPc not only shows a photodynamic effect of destroying malignant tumors by generating cytotoxic reactive oxygen species, but also has a large light absorption cross-section in the tissue transmission spectral wavelength range of 650-900 nm. However, a decisive limitation to the practical application of ZnPc is its high hydrophobic feature which leads to poor solubility in body fluids. Accordingly, various approaches have been developed to overcome these obstacles, for example, ZnPc derivatives with improved water solubility and transporters that enable transport ZnPc. However, these methods require complex post-processing operations, which may produce various by-products and lead to unavoidable damage. Previously, the present inventor reported high-quality α-form ZnPc nanowires (NWs) exhibiting improved water dispersibility and efficiency dual photodynamic and photothermal performance, all of which have synergistic effects in cancer phototherapy in vitro and in vivo. However, the difficult phase separation of α-form and β-form ZnPc obtained simultaneously still remains a great limitation in actual anticancer substances because the presence of a small amount of R-form ZnPc causes aggregation and precipitation in solution. Accordingly, the growth of high-quality and high-yield α-form ZnPc NWs is an important and urgent problem for practical applications including clinical trials. In this regard, the present inventor focused on the development of an easy and efficient method for the selective growth of α-form ZnPc NWs. In various Pc studies, it is well known that a crystalline phase is closely related to a crystal size. However, solution-phase crystallization is difficult to control the crystal size without the use of additional chemicals such as capping agents or surfactants. Accordingly, the PVT method, which is a gas phase crystallization method suitable for obtaining pure and high-quality crystals, was used, and it was identified that the flow speed of carrier gas was closely related to the size of the crystals prepared. By increasing the flow speed of the carrier gas, it is possible to successfully reduce the crystal size of ZnPc NWs and grow α-form ZnPc NWs with high yield. In particular, β-form ZnPc NWs grown at a carrier gas flow speed of 2000 sccm exhibited very high water dispersibility without significant agglomeration after dispersing in water for 8 hours.

In particular, in Korean Patent No. 10-1352931, which is a related document of the present invention, the flow speed of carrier gas carrying vaporized phthalocyanine was merely 800 sccm, and the weight % of the α-form of phthalocyanine prepared through this preparation process was actually 90% by weight, hence, a significant β-form phthalocyanine compound was included. Thus, there was a limitation in that water dispersibility was relatively poor.

In this regard, the present inventor developed a high-purity, high-yield phthalocyanine compound after observing that the ZnPc NW of the present invention may be used for understanding the crystallization of molecules, in particular, controlling the crystal structure of crystals and commercializing actual cancer treatment, and then completed the invention.

DISCLOSURE Technical Problem

The present invention is directed to providing a method of preparing M-phthalocyanine nanowires, in which the method includes:

1) vaporizing M-phthalocyanine, in which the M is zinc or copper;

2) transporting the vaporized M-phthalocyanine of operation 1) using an inert gas, in which a flow speed of the inert gas is in the range of 1900 to 2100 sccm; and

3) collecting the transported vaporized M-phthalocyanine of operation 2) and precipitating the same in an M-phthalocyanine crystal form.

In addition, the present invention is directed to providing M-phthalocyanine nanowires prepared by the above preparation method.

Technical Solution

One aspect of the present invention is directed to providing a method of preparing M-phthalocyanine nanowires, in which the method includes:

1) vaporizing M-phthalocyanine, in which the M is zinc or copper;

2) transporting the vaporized M-phthalocyanine of operation 1) using an inert gas, in which a flow speed of the inert gas is in the range of 1900 to 2100 sccm; and

3) collecting the transported vaporized M-phthalocyanine of operation 2) and precipitating the same in an M-phthalocyanine crystal form.

The phthalocyanine of the present invention has a chemical structure of a compound of Formula 1 below.

In a specific embodiment, the M of M-phthalocyanine may be in a form bonded to four nitrogen atoms inside phthalocyanine as in a compound of Formula 2 below.

The M may be zinc or copper, but is not limited thereto.

In the operation of transporting the vaporized M-phthalocyanine compound of the operation 2) using an inert gas, a weight percentage of α-form M-phthalocyanine crystals may be selectively controlled by controlling a flow speed of the inert gas.

A preferred example of the inert gas is argon gas, and an inert gas that may be used as a carrier gas for condensing and recrystallizing vaporized M-phthalocyanine may be freely used.

The flow speed of the inert gas may be in the range of 1900 to 2100 sccm, preferably in the range of 1950 to 2050 sccm, and most preferably in the range of 2000 sccm. By controlling the flow speed of the inert gas within the above range, the weight of the α-form M-phthalocyanine crystal of the following Formula 3 may be selectively controlled.

The M-phthalocyanine compound of the operation 1) is characterized in that the alpha (α)-form M-phthalocyanine nanowire according to the present invention is obtained by vapor-condensation-recrystallization (VCR) of M-phthalocyanine. More specifically, the alpha (α)-form M-phthalocyanine nanowire may be obtained by condensing and recrystallizing the evaporated vapor on a substrate at a temperature lower than the heating temperature, for example, room temperature to 80° C. by heating the raw material M-phthalocyanine (for example, in a powder state) to 470 to 700° C., preferably 470 to 600° C., or more preferably 500° C., and by growing M-phthalocyanine in the form of nanowires on the substrate. The diameter of the α-form M-phthalocyanine nanowire thus obtained may be about 30 to 50 nm, and the length may be about 1 to 10 m.

The collection in the operation 3) may be condensing and recrystallizing on a Si(100) substrate at room temperature to 80° C.

In addition, the α-form M-phthalocyanine nanowire, unlike the conventional phthalocyanine powder, has very excellent solubility and dispersibility in water, and is characterized in that stability in aqueous solution is remarkably improved (maintaining stability in aqueous solution for 3 months or more). The aqueous solubility of α-form M-phthalocyanine nanowires may be further enhanced through agitation such as sonication. The solubility and dispersibility in water of the thus obtained α-form M-phthalocyanine nanowire is possible up to 120 mg/L at room temperature.

Another aspect of the present invention is directed to providing M-phthalocyanine nanowires prepared by the above method.

The M-phthalocyanine nanowire may include 95% by weight or more of α-form crystals, and preferably 98% by weight or more of α-form crystals. The weight of the crystal form may be controlled by adjusting the flow speed of the inert gas to an appropriate range as described above.

The M-phthalocyanine compound is mainly a mixed crystal form of α and β forms, mainly α-form having the crystal structure of Formula 3 above. The α-form crystals are the major phase constituting at least 50% of the crystalline forms. Since the presence of the β-form phthalocyanine causes aggregation and precipitation in solution, it may contain 95% by weight, preferably 98% by weight or more, and most preferably more than 98% by weight of α-form crystals to maintain excellent water dispersibility.

Overlapping contents are omitted in consideration of the complexity of the present specification, and terms not defined otherwise in the present specification have the meanings commonly used in the technical field to which the present invention pertains.

Advantageous Effects

M-phthalocyanine nanowires according to the present invention can have a variety of uses as the M-phthalocyanine nanowires can control the crystalline structure thereof by controlling the flow speed of a carrier gas to a suitable range, and can exist in hydrophilic solvent without agglutinating due to superb dispersibility in water.

DESCRIPTION OF DRAWINGS

FIG. 1 shows an experimental plan and morphology of ZnPc crystals grown under different flow speed conditions, respectively. (A) Schematic diagram of the PVT system used to grow ZnPc crystals. SEM images of ZnPc crystals grown with carrier gas flow speeds of (B) 50 sccm, (C) 200 sccm, (D) 800 sccm, and (E) 2000 sccm are shown.

FIG. 2 relates to a crystal structure analysis of α-form ZnPc crystals. (A) PXRD patterns of ZnPc crystals grown under different flow speed conditions, (B) low-magnification TEM images, (C) high-resolution TEM images of α-form ZnPc NWs ([100] SAED pattern of ZnPc NWs by projection), (D) a laminated arrangement of α-form ZnPc crystals along the normal direction of plane molecules, (E) a magnified image of (C), and (F) a schematic diagram of successive lamination layers of ZnPc molecules for [100] projection are shown.

FIG. 3 relates to a statistical study of ZnPc crystals obtained according to the water dispersibility test and flow speed, each of which shows (A) images of ZnPc crystals dispersed in water according to the flow speed of carrier gas, and (B) statistical width and α-type wt % trend of ZnPc crystals grown under different flow speed conditions.

FIG. 4 shows a TEM image of an α-form ZnPc nanowire having the thinnest width (12 nm) obtained at a flow speed of 2000 sccm.

FIG. 5 relates to an analysis of the crystal structure of the β-form ZnPc nanowire, and shows (A) a low magnification TEM image and (b) a high magnification TEM image.

FIG. 6(A) is a schematic diagram for obtaining an α-form ZnPc reference solution, (B) shows images of α-form ZnPc and the reference solution extracted at various concentrations, (C) shows a PXRD pattern of the extracted α-form ZnPc, (D) shows a UV-VIS spectrum of the reference solution, and (E) shows a linear fitting graph between the absorbance and concentration of the α-form ZnPc reference solution.

FIG. 7 shows SEM images of CuPc crystals grown at a flow speed of (A) 50 sccm, (B) 200 sccm, (C) 800 sccm, and (D) 2000 sccm.

FIG. 8 shows images of CuPc crystals dispersed in water according to the flow speed of the carrier gas.

FIG. 9 shows a PXRD pattern of CuPc nanowire crystals grown at different flow speeds.

MODES OF THE INVENTION

Hereinafter, preferred examples are presented to help the understanding of the present invention. However, the following examples are only provided for easier understanding of the present invention, and the content of the present invention is not limited by the examples.

EXAMPLES Example 1. Preparation of ZnPc and CuPc Nanowires and Analysis of Changes in Characteristics of Nanowires According to Carrier Gas Flow Speeds

By using ZnPc powder as a precursor, alpha (a) type ZnPc nanowires were prepared through physical vapor transport called vaporization-condensation-recrystallization (VCR).

ZnPc nanowires and CuPc nanowires were prepared using commercially available zinc phthalocyanine (ZnPc, 97%, Sigma-Aldrich) and copper phthalocyanine (CuPc, 97%, Sigma-Aldrich) precursors, respectively, without further purification. Specifically, ZnPc or CuPc powder (0.02 g, Sigma-Aldrich) was loaded into a ceramic boat located at the center of a quartz tube in an electric heating system. About 20 mg of precursor loaded into a ceramic boat was placed in the center of the tube furnace using a quartz protective tube. A piece of Si substrate was placed at the end of a quartz tube, where the temperature was naturally reduced below 80° C. to effectively collect the crystals. After flushing the quartz tube with Ar gas at a flow speed of 1000 sccm for 5 minutes, the furnace temperature was increased up to 500° C. under specific Ar flow speeds (50, 200, 800, 2000 sccm). After reacting at the target temperature for 10 minutes, the furnace was turned off to allow the furnace to naturally cool to room temperature. Such a VCR process is schematically shown in FIG. 1(A).

The morphology of the prepared crystals was analyzed by scanning electron microscopy (SEM, JSM-7401F, JEOL). To prevent electronic charging of the crystal, platinum was coated to create a conductive layer on the crystal surface. In addition, X-ray diffraction patterns of ZnPc and CuPc crystals were obtained from the 5D beamline of PAL (Pohang Accelerator Laboratory). All data obtained were converted to the wavelength of CuKα (λ=1.541841 Å) for better comparison with the reference. A high-resolution transmission electron microscope (HRTEM, JEM-2200FS, JEOL) was used for structural analysis, and samples for TEM measurement were prepared by stamping ZnPc crystals onto a carbon-coated Cu grid.

The stability of α- and β-form ZnPc crystals is affected by crystal size due to their lattice potential and surface energy. According to Buckingham's equation used to estimate the interatomic unbonding potential of organic molecular crystals, α-form ZnPc is more stable than β-form when the crystal size is smaller. In general, in the case of a vapor deposition process, the crystal size is greatly affected by the flow speed of the carrier gas. Accordingly, the flow speed of argon gas was adjusted from 50 to 2000 sccm to selectively obtain α-form ZnPc crystals. FIGS. 1B to 1E show SEM images of ZnPc crystals obtained in argon gas at different flow speeds. As the flow speed increased, the crystal width decreased from about 460 nm (at 50 sccm (FIG. 1(B)) to 35 nm (at 2000 sccm (FIG. 1(E)). To identify the crystal structure of the obtained ZnPc crystal, the present inventor measured powder X-ray powder diffraction (PXRD) and high-resolution transmission electron microscopy (HR-TEM). FIG. 2(A) shows PXRD spectra of crystals grown under different flow speed conditions. Due to the different packing structures of α-form and β-form ZnPc crystals, X-ray diffraction patterns with each different characteristic were shown. One of the representative characteristic diffraction planes of the α and β forms of ZnPc crystals are the (002) and (202) planes showing diffraction peaks at 2θ=7.712 and 2θ=18.783, respectively. In the case of the ZnPc crystal grown at a flow speed of 50 sccm (black line in FIG. 2(A)), the diffraction peak of the (202) plane of the β-form was clearly shown, and the (002) plane of the α-form was absent, which means that the β-form ZnPc crystals are obtained predominantly in the carrier gas at a relatively low flow speed. On the other hand, as the (202) diffraction peak of the β-form gradually decreased and the flow speed increased, the (002) peak observed in the α-form appeared newly. At a flow speed of 2000 sccm (red line in FIG. 2(A)), a clear (002) diffraction plane of α-form and disappearance of a (202) diffraction plane of β-form was observed, which indicates that the α-form ZnPc crystal selectively grows at a relatively high flow speed. These results showed that the crystalline phase of ZnPc may be successfully controlled by changing the flow speed of the carrier gas in the PVT method.

Example 2. Crystal Structure Analysis of ZnPc Crystals

The characteristic crystal planes of α-form and β-form ZnPc crystals were also identified through TEM measurement. FIG. 2(B) shows a low magnification image of α-form ZnPc NWs with a uniform surface with a width of about 50 nm and a length of the scale of several micrometers. The present inventor noted that the width of the thinnest NW obtained at a flow speed of 2000 sccm was about 15 nm, specifically 12 nm (FIG. 4 ). FIGS. 2(C) and 2(E) are HR-TEM images of α-form ZnPc NWs showing well-defined crystal planes. FIG. 2(C) is an electron diffraction pattern of NWs showing a clear diffraction spot with a lattice distance of 1.134 nm which is in good agreement with the distance of the (002) diffraction plane observed in the PXRD pattern of FIG. 2(A) (d(002)=11.464 Å at 2θ=7.712). FIG. 2(E) is an enlarged image of the (002) lattice corresponding to the aligned Zn ions as described by the red line in FIG. 2(F). FIG. 2(D) is the molecular structure and detailed staking arrangement of α-form ZnPc along the b-axis, which shows the growth direction of ZnPc NWs along the stacked [010] direction by π-π interactions. The biggest difference in the molecular packing structure of a and β-form ZnPc is the angle between the column direction (b axis) and the normal direction of the planar ZnPc molecule. Due to the smaller angle (

25°) of the α-form than that of the ZnPc β-form (≈45°), the zinc and nitrogen atoms of the α-form ZnPc NW may use bonding sites that may interact with water molecules by coordination and hydrogen bonding. On the other hand, the water molecule forms a coordination bond between the Zn (II) ion and the ZnPc adjacent to the nitrogen atom. In addition, a well-defined single crystal structure of the β-form ZnPc crystal was identified (FIG. 5 ). The lattice distance of the (202) plane of the β-form is 0.480 nm, which is in good agreement with the PXRD result of FIG. 2(A) (2θ=18.783 at d(202)=4.724 Å). From the crystal structure analysis of the ZnPc crystals obtained under each flow speed condition, direct evidence was first identified for the relationship between the crystal phase and the carrier gas flow speed, which was the key for the selective growth of α-form ZnPc.

Example 3. Water Dispersibility Test and Statistical Analysis of ZnPc and CuPc Crystals

ZnPc and CuPc nanowire dispersion aqueous solution was prepared by adding crystals collected on a Si substrate to water and then sonicating in a bath sonicator (UCS-10, JEIOTECH) for 40 minutes. For the quantitative analysis of α-form ZnPc crystals obtained at different flow speeds, the present inventor used the unique light absorption band of α-form measured using a UV-VIS spectrometer (UV-2600, SHIMADZU). In order to obtain reference data indicating the relationship between the concentration and absorbance of the α-form, the α-form ZnPc was isolated from the ZnPc solution stored for 24 hours after dispersing the ZnPc in deionized water. A schematic diagram of the experimental process is shown in FIG. 7(A). The isolated α-form ZnPc showed a characteristic diffraction pattern of the α-form (FIG. 7(C)), and the UV-VIS spectra of the five reference solutions showed the same peak position and increased absorption intensity as the concentration increased. (FIG. 7(D)) The concentration and absorbance showed a linear relationship as shown in FIG. 3(E).

Based on the reference data, the concentration of α-form ZnPc in each solution obtained at different flow speeds was determined by measuring the light absorbance at 730 nm of the upper (well-dispersed) portion of the ZnPc solution stored for 8 hours. By matching the absorbance of the solution of interest with the reference linear fitting data shown in FIG. 7(E), the concentration of α-form ZnPc was multiplied by the volume of water to calculate the weight % of α-form ZnPc at each flow speed condition.

The biggest advantage of α-form ZnPc is that the water dispersibility is greatly improved. To identify the water dispersibility of the ZnPc and CuPc crystals obtained under different flow speed conditions, equal amounts of each product were dispersed in deionized water (DI). The upper portion of FIG. 3(A) is a photograph of a solution obtained after 40 minutes of sonication to uniformly disperse ZnPc. Except that the leftmost solution prepared using the ZnPc crystal obtained at a flow speed of 50 sccm had a light blue color, the other solutions showed a similar dark blue color. After storage for 8 hours at ambient conditions, the ZnPc solution prepared by crystals obtained at a flow speed of 50 sccm showed strong precipitation, and the amount of precipitation decreased as the flow speed increased. (Bottom of FIG. 3(A)) In particular, a solution prepared using ZnPc crystals obtained at a flow speed of 2000 sccm (rightmost of FIG. 3(B)) exhibited improved water dispersibility without significant precipitation. These results were in good agreement with the PXRD data in which the proportion of α-form ZnPc increased as the carrier gas flow speed increased.

For quantitative analysis of α-form ZnPc in each solution, the UV-VIS spectrum of the solution remaining after separation of the precipitate (β-form ZnPc) was measured (FIG. 6(D)). Using the characteristic absorption peak of α-form ZnPc at 780 nm, the weight percentage of α-form ZnPc in solution was calculated by comparing the peak intensity with the absorption spectrum of a reference solution. As expected from the PXRD data (FIG. 2(A)), the calculated weight percent of α-form ZnPc in the product increased as the flow speed of the carrier gas increased (blue line in FIG. 3(B)). In addition, surprisingly, at a flow speed of 2000 sccm, the percentage of α-form exceeded 98%. The black line in FIG. 3(B) shows the relationship between the average width and the flow speed of ZnPc crystals that decrease as the flow speed increases from 460 nm (50 sccm) to 35 nm (2000 sccm). By comparing and analyzing the above three important values, average width, percentage and flow speed of carrier gas of α-form ZnPc NWs, it was clearly identified that α-form ZnPc grew significantly favorably in carrier gas with high flow speed, which effectively reduces the width of NWs.

Example 4. Analysis of Characteristics of CuPc Nanowires According to Carrier Gas Flow Speed

To identify various uses, it was attempted to control the phase of copper phthalocyanine (CuPc), which is well-known as an excellent hole injection material for light-emitting diodes. Due to its low solubility in organic solvents that are different from water, uniform coating of CuPc on a target substrate is one of the major limitations in device application. Accordingly, the water dispersibility of CuPc was improved by reducing the size of CuPc crystals by controlling the flow speed of the carrier gas. Similar to ZnPc, CuPc exhibited a nanowire-like morphology and width of CuPc NWs, which were successfully reduced by increasing the flow speed of the carrier gas (FIG. 7 ). Through the water dispersibility test, it was identified that CuPc NWs grown in a high flow speed carrier gas had excellent water dispersibility. From the results of FIG. 8 , the present inventor was convinced that the flow speed control method is applicable to various Pc crystals.

In summary, the inventor of the present invention successfully obtained a high yield of α-form ZnPc NWs exhibiting high water dispersibility without agglomeration or significant precipitation. The selective growth of α-form ZnPc NWs is achieved by controlling the flow speed of the carrier gas in the PVT method. Through morphological observation and crystal structure analysis, it was demonstrated that the width of ZnPc crystals was successfully controlled by the flow speed of carrier gas, which affects the phase of ZnPc crystals. Through UV-VIS analysis of crystals grown at a flow speed of 2000 sccm, it was identified that 98% or more of ZnPc crystals were α-form ZnPc. Accordingly, the results of the present invention demonstrate that flow speed control may be an effective method to obtain ZnPc crystals with desired phases. 

1. A method of preparing M-phthalocyanine nanowires, the method comprising: 1) vaporizing M-phthalocyanine, wherein the M is zinc or copper; 2) transporting the vaporized M-phthalocyanine of operation 1) using an inert gas, wherein a flow speed of the inert gas is in a range of 1900 to 2100 sccm; and 3) collecting the transported vaporized M-phthalocyanine of the operation 2) and precipitating the same in an M-phthalocyanine crystal form.
 2. The method of claim 1, wherein the M-phthalocyanine compound of the operation 1) is vaporized at a temperature of 470 to 700° C.
 3. The method of claim 1, wherein the collection in the operation 3) is condensing and recrystallizing on a Si(100) substrate at room temperature to 80° C.
 4. The method of claim 1, further comprising sonification step after the operation 3).
 5. The method of claim 1, wherein a diameter of the prepared M-phthalocyanine nanowire is 30 to 50 nm, and a length thereof is 1 to 10 μm.
 6. M-phthalocyanine nanowires prepared by the preparation method of claim
 1. 7. The M-phthalocyanine nanowires of claim 6, wherein the M-phthalocyanine nanowires include 95 wt % or more of α-form crystals of following Formula (3):


8. The M-phthalocyanine nanowires of claim 6, wherein the M-phthalocyanine nanowires include 98 wt % or more of α-form crystals of following Formula (3): 